ROC Curve Construction Research Articles

DETERMINATION OF THE LEVEL OF CIRCULATING ENDOTHELIAL CELLS AND THE EXPRESSION OF ADHESIVE P-SELECTIN AS PROGNOSTIC MARKERS OF THE SEVERITY OF PSORIASIS

Introduction. Psoriasis is one of the most pressing problems of dermatologists, it accounts for up to 30% of all skin diseases. The study of the pathogenesis of psoriasis is currently due to an increase in the number of severe, disabling forms of the disease. The purpose of the study. To evaluate the prognostic significance of markers of endothelial dysfunction and platelet functional activity in patients depending on the severity of psoriasis. Materials and methods. The study included 80 patients with vulgar psoriasis (40 women and 40 men) with a course of moderate severity (n=33, PASI – 17±5, DLQI-7±2)), and severe (n=47, PASI -30±7, DLQI-16±3). The average age is 48±15 years. Circulating endothelial cells and P-selectin on platelets were determined on an FC500 flow cytometer (Beckman Coulter). Results. In patients with moderate and severe psoriasis, a statistically significant increase in the level of circulating endothelial cells was found (10 [7.5-11.5]/3x105 WBC) and (14 [7.0-19.5]/3x105 WBC), respectively, compared with the control group (3.0 [1.0-5.0]/3x105 WBC), p 0.001. The number of platelets with P-selectin expression (1.9% [1.25-2.65]) in patients with moderate severity and (3.2% [1.5-5.4]) with severe course was significantly higher than in the control group (0,9% [0,7-1,7]). Correlation analysis showed that the level of P-selectin is directly correlated with the level of circulating endothelial cells. To increase the prognostic significance of these laboratory parameters and assess the severity of the condition, a ROC analysis was performed with the construction of ROC curves and the calculation of the area under the curve (AUC). Conclusion. It was found that the level of P-selectin is a more sensitive prognostic marker of the severity of psoriasis, and the number of circulating endothelial cells is a specific prognostic marker for the development of possible cardiovascular outcomes.

Evaluation of gut microbiota predictive potential associated with phenotypic characteristics to identify multifactorial diseases

ABSTRACT Gut microbiota has been implicated in various clinical conditions, yet the substantial heterogeneity in gut microbiota research results necessitates a more sophisticated approach than merely identifying statistically different microbial taxa between healthy and unhealthy individuals. Our study seeks to not only select microbial taxa but also explore their synergy with phenotypic host variables to develop novel predictive models for specific clinical conditions. Design: We assessed 50 healthy and 152 unhealthy individuals for phenotypic variables (PV) and gut microbiota (GM) composition by 16S rRNA gene sequencing. The entire modeling process was conducted in the R environment using the Random Forest algorithm. Model performance was assessed through ROC curve construction. Results: We evaluated 52 bacterial taxa and pre-selected PV (p < 0.05) for their contribution to the final models. Across all diseases, the models achieved their best performance when GM and PV data were integrated. Notably, the integrated predictive models demonstrated exceptional performance for rheumatoid arthritis (AUC = 88.03%), type 2 diabetes (AUC = 96.96%), systemic lupus erythematosus (AUC = 98.4%), and type 1 diabetes (AUC = 86.19%). Conclusion: Our findings underscore that the selection of bacterial taxa based solely on differences in relative abundance between groups is insufficient to serve as clinical markers. Machine learning techniques are essential for mitigating the considerable variability observed within gut microbiota. In our study, the use of microbial taxa alone exhibited limited predictive power for health outcomes, while the integration of phenotypic variables into predictive models substantially enhanced their predictive capabilities.

Возможности ультразвук-ассистированного осмотра в оценке суставного синдрома

Ultrasound (US) of joints is a fast, accessible, cost-effective, informative method of examination. US-assisted examination of joint allows a clinician to assess the joint condition at the patient’s bedside as part of an objective examination. The purpose — to evaluate the reproducibility of ultrasound-assisted joint examination in rheumatology in comparison with expert class ultrasound. Material and methods. We compared the capabilities of expert-class ultrasound with ultrasound-assisted examination by 5 parameters (presence of effusion into the joint cavity, synovial vascularization, erosions, osteophytes and extensor muscle tenosynovitis) during ultrasound examination of wrist joints in 22 patients with rheumatoid arthritis. Statistical analysis included Cohen’s kappa counting and construction of ROC curves by logistic regression method. Results. Ultrasound-assisted examination is comparable to expert-class ultrasound in evaluating the inflammatory pattern. At the same time, ultrasound-assisted examination showed moderate comparability in evaluating degenerative changes and low comparability in evaluating destructive changes.

Application of roc-analysis to assess the quality of predicting the risk of chronic rhinosinusitis recurrence

Aim: To propose a new, original approach to assessing the quality of a multivariate regression model for predicting the risk of recurrence in patients with chronic rhinosinusitis based on ROC analysis with the construction of appropriate curves, estimating the area under them, as well as calculating the sensitivity, accuracy, specificity, and predictive value of a positive and negative classification results, the likelihood ratio of positive and negative patient detection results. Materials and Methods: 204 patients aged with a diagnosis of chronic rhinosinusitis were examined. Results: To build a multivariate regression model 14 probable factors of chronic rhinosinusitis occurrence were selected to determine the diagnostic value of the proposed model we calculate the sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), the likelihood ratio of a positive test (LR+), the likelihood ratio of a negative test (LR-) and prediction accuracy % of the proposed mathematical model. In order to determine the prognostic value of the risk ratio of CRS recurrence model, ROC- analysis was performed, ROC curves were obtained Conclusions: The multivariate regression model makes it possible to predict potential complications and the possibility of disease recurrence. The construction of ROC-curves allows us to assert the excellent classification quality of chronic rhinosinusitis recurrence.

Identification of cuproptosis-related gene SLC31A1 and upstream LncRNA-miRNA regulatory axis in breast cancer

Mounting evidence indicate that cuproptosis, a novel form of programmed cell death, contributes to cancer development and progression. However, a comprehensive analysis regarding the expressions, functions, and regulatory network of cuproptosis-related genes is still lacking. In the present work, cuproptosis-related genes, upstream miRNAs and lncRNAs, and clinical data of breast cancer from TCGA database were analyzed by R language including Cox regression analysis, correlation calculation, ROC curve construction, and survival evaluation, and were further verified by public-available databases. Chemosensitivity and immune infiltration were also evaluated by online tools. SLC31A1 was significantly increased in breast cancer samples than those in normal tissues. SLC31A1 was negatively related to a favorable outcome in breast cancer, and the AUC value increased with the prolongation of follow-up time. LINC01614 and miR-204-5p were potential upstream regulators of SLC31A1. Moreover, SLC31A1 was significantly positively correlated with different immune cells infiltration, immune cell biomarkers, and immune checkpoints in breast cancer. SLC31A1 was a potential cuproptosis-related gene in breast cancer, which was significantly upregulated and was able to predict diagnosis, prognosis, chemosensitivity, and immune infiltration. LINC01640/miR-204-5p/SLC31A1 might be a significant and promising axis during cuproptosis in breast cancer.

Serum Metabolomics Analysis of Skin-Involved Systemic Lupus Erythematosus: Association of Anti-SSA Antibodies with Photosensitivity.

Systemic lupus erythematosus is a heterogeneous autoimmune disease in which skin involvement is a common manifestation. It is currently thought that the photosensitivity of SLE skin involvement is associated with anti-SSA antibodies. This study aimed to expand the current state of knowledge surrounding the molecular pathophysiology of SLE skin photosensitivity through Serum metabolomics analysis. The serum metabolites of 23 cases of skin-involved SLE (SI) group, 14 cases of no SI (NSI) group, and 30 cases of healthy controls (HC) were analyzed by using UPLC-MS/MS technology, and subgroup analysis was performed according to the expression of anti-SSA antibodies in SI. MetaboAnalyst 5.0 was used for enrichment analysis and ROC curve construction, identifying serum metabolic markers of skin-involved SLE associated with anti-SSA antibodies. We identified several metabolites and metabolic pathways associated with SLE photosensitivity. Two metabolites, SM (d18:1/24:0) and gamma-CEHC can distinguish between anti-SSA antibody-positive and negative SI, with AUC of 0.829 and 0.806. These two photosensitization-related substances may be potential markers of skin involvement in SLE associated with anti-SSA antibody. This study provides new insights into the pathogenesis of SI patients, and provides a new molecular biological basis for the association between anti-SSA antibodies and skin photoallergic manifestations of SLE.

Evaluation of vitamin A and E deficiency with severity of SARS-COV-2 disease: a case–control study

BackgroundCoronavirus disease 2019 can cause severe inflammation and damage to the lungs. Vitamins A and E are essential in the enhancement of immunity and they tend to decrease in cases with inflammation. Determination of serum levels of vitamins A and E in COVID-19 patients was the aim of the study.MethodsThis case–control study was carried out on 30 ICU–admitted SARS-CoV-2–infected individuals (group A), 30 ward–admitted SARS-CoV-2–infected individuals (group B) and 30 healthy controls (group C). High-performance liquid chromatography was used to measure vitamin A and E levels.ResultsMedian levels of vitamin A in group A [0.16 (0.08–0.23) µg/ml] were significantly lower than those in group B [0.4 (0.15–0.65) µg/ml] and in group C [0.81 (0.70–1.16) µg/ml] with P value < 0.001, while there was no significant difference between groups concerning vitamin E levels (P value = 0.535). Vitamin A deficiency showed significant correlation with lower hemoglobin levels, lower platelet counts, higher total leucocyte counts, higher C- reactive protein levels, and higher D-dimer levels. ROC curve construction showed that vitamin A level with cut off < 0.65 µg/ml increases risk of acute respiratory distress syndrome (ARDS) development with sensitivity 90% and specificity 83.3%. Logistic regression analysis showed that cases with vitamin A levels < 0.65 µg/ml were more prone to develop ARDS (OR = 0.003 [0.000–0.036] P < 0.001).ConclusionLevels of vitamin A were reduced in COVID-19 patients particularly in ICU–admitted cases. This ensures the association of decreased vitamin A with disease morbidity and the importance of vitamin A supplementation as part of disease management.Trial registrationClinicaltrial.gov, NCT05946499. Registered 12 July 2023—Retrospectively registered. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000DGLS&selectaction=Edit&uid=U00070DC&ts=2&cx=gieusm.

Blood Serum Zonulin in Colorectal Cancer, Autoimmune Bowel Diseases, and Irritable Bowel Syndrome.

Zonulin content in blood serum of patients with colorectal cancer (CRC; n=152; 30-84 years) and patients with large bowel adenomas (n=32; 39-82 years) was measured by standardized kit IDK Zonulin ELISA (Immundiagnostik AG). The healthy control group (n=50) comprised volunteers (27 women, 23 men; 25-68 years); pathological control group (n=84) - patients (55 women, 29 men;18-84 years) with irritable bowel syndrome (n=29), Crohn's disease (n=5), and ulcero-necrotic colitis (n=50). In comparison to healthy control group, the level of zonulin was significantly increased in CRC patients (p<0.0000001) and in patients with benign large bowel tumors (p<0.004), as well as in patients with inflammatory intestine diseases and with irritable bowel syndrome (p<0.0002). Zonulin level in blood serum of CRC patients was slightly, but significantly higher (p<0.05) than in the group of pathological control. ROC curve construction revealed that at optimal zonulin cut-off level (52.2 ng/ml), the diagnostic sensitivity of CRC detection was 66.7% and specificity relative to healthy control was 81.8%. The specificity relative to the combined control group (healthy control+non-tumor bowel diseases) was only 68.9%. Thus, no acceptable cut-off levels for differentiation between malignant and benign tumors, as well as between tumor and non-tumor large bowel pathologies were found. Analysis of the associations between serum zonulin level and the main clinical and pathological characteristics of CRC demonstrated that the level of this marker increased with disease progression (p<0.01; Kruskal-Wallis test), but was not associated with individual criteria of the TNM system, tumor localization, histological structure, and malignancy grade.

РАЗРАБОТКА ПРОГНОСТИЧЕСКОЙ МОДЕЛИ ДЛЯ ВЫБОРА МЕТОДА КИШЕЧНОГО АНАСТОМОЗА У ДЕТЕЙ С НАИЛУЧШЕЙ ПРОГНОСТИЧЕСКОЙ СИЛОЙ НА ОСНОВЕ ROC-AUC

Objective of the study: development of mathematical models to assess the method of formation of the intestinal anastomosis with a comparison of the effectiveness of these models. Materials and methods of research: from January 2012 to December 2019, 204 operations were performed to restore the continuity of the intestinal lumen, of which 126 were performed using a stapler, 78 – using manual techniques. 90 of the 204 patients were girls (44.1%) and 114 were boys (55.9%). The age of the patients varied from 1 to 322 days, weight – from 950 to 7900 g, the minimum gestational age – from 22 to 42 weeks. To determine the method of intestinal anastomosis formation, the following mathematical models were used: binary logistic regression, binary logistic regression with the method of stepwise inclusion based on maximum likelihood (Forward: LR), neural network. In the first method of calculations, all variables declared as covariates were simultaneously involved in the calculation. The second method – Forward: LR, started by using only constants at the start, and then sequentially connected variables that demonstrate a strong relationship with dependent variables. The third method is a neural network. A radial basis function was used as a mathematical basis for constructing a neural network. To train the neural network, the active dataset was divided into training, validation and control samples. Observations were randomly divided based on relative numbers (50%, 25% and 25%). Results: 3 patients with different initial data were selected for a comparative analysis of the three mathematical models. Evaluation of the effectiveness of the obtained mathematical models was based on the construction of ROC curves. It was found that for the binary logistic regression the area under the ROC curve was 0.975, for the binary logistic regression with the stepwise inclusion method based on the maximum likelihood (Forward: LR) the area under the ROC curve was 0.975, for the radially basic neural network the area under the ROC curve amounted to 0.888. Conclusions: the quality of the doctor's work can be confirmed by methods of mathematical modeling. The choice of surgical intervention is implemented by three mathematical models and their qualitative assessments are given. The developed integrated approaches can be made available to specialists in subject areas for use in clinical practice, as well as for machine learning and the creation of future automated systems based on intelligent mathematical technologies.

ПРОГНОЗ ИСХОДА ВТОРИЧНОГО ПЕРИТОНИТА

Objectives. To develop a new system for predicting the outcome of secondary peritonitis and analyze its accuracy in comparison with the most common analogous systems. Methods. The study is based on the analysis of treatment results in patients (n=352) with secondary peritonitis. At admission sepsis was diagnosed in 15 (4.3%) patients, septic shock - in 4 (1.1%) persons. There were the following main causes of death in the mortality structure: purulent intoxication and/or sepsis - 51 cases (87.9%), cancer intoxication - 4 (6.9%) cases, acute cardiovascular failure - 3 cases (5.2%). The efficacy of the Mantheim Peritoneal Index (MPI), WSES prognostic score, APACHE-II scale, gSOFA score and Peritonitis Prediction System (PPS) developed by the authors were analyzed. The likelihood of the effect of 85 clinical and laboratory parameters on the outcome of patients with secondary peritonitis using nonparametric methods of statistical research (Fisher’s test, Mann-Whitney test, Chi-square with Yates correction) have been analyzed. Criteria predictively associated with lethal outcome (p &lt;0.05) were selected, they were included in the PPS scale. To compare the predictive value of peritonitis prediction systems, ROC analysis was used with the construction of ROC curves for each of the systems. Results. The most important criteria in predicting fatal outcome are the patient’s age, the presence of malignant tumor, the exudate nature, sepsis (septic shock), and also polyorganic insufficiency which is not associated with developed peritonitis. To assess the prognostic value of peritonitis prediction systems, ROC curve analysis was used. The greatest accuracy in terms of predicting mortality in patients with generalized secondary peritonitis is possessed by PPS (AUC 0.942), minimal - APACHEII (AUC 0.840). Conclusion. APACHEII, MPI, WSESSSS and PPS systems can be considered as reliable in predicting mortality in patients with peritonitis. The greatest accuracy in predicting fatal outcome in patients with generalized secondary peritonitis had PPS (94%). What this paper adds An original system for predicting the outcome of peritonitis (PPS) has been developed. It was found that the criteria of the patient’s age, the presence of a malignant neoplasm, the nature of the exudate, sepsis (septic shock), as well as polyorganic insufficiency not associated with the developed peritonitis are of the greatest importance in predicting the death outcome. When conducting a comparative assessment with the most common similar systems (MPI, WSES SSS, APACHE-II), it was found that the most accurate in terms of predicting mortality in a patient with generalized secondary peritonitis is the PPS (AUC 0.942), the minimum - APACHEII (AUC 0.840).

Correlations between clinical and laboratory findings and prognostically unfavorable CMR-based characteristics of acute ST-elevation myocardial infarction.

Aim To evaluate factors associated with unfavorable predictive characteristics of ST-segment elevation acute myocardial infarction (STEMI) as per data of magnetic resonance imaging (MRI).Material and methods The study included 52 patients with STEMI who underwent a primary percutaneous coronary intervention (pPCI). Contrast-enhanced cardiac MRI was performed for all patients on days 3-7. Delayed contrast-enhancement images were used for assessing infarct size, presence of microvascular obstruction (MVO) areas, and heterogeneity zones.Results Multifactorial analysis showed that independent predictors of MVO were type 2 diabetes mellitus (DM) (relative risk (RR) 1.9, confidence interval (CI): 1.1-3.26, р=0.012), increased levels of brain natriuretic peptide (BNP) (RR 2.04, CI: 1.39-2.99, р=0.004) and creatine kinase (CK) (RR 2.06, CI: 0.52-0.80, р=0.02), and infarct size (IS) (RR 2.81; CI: 1.38-5.72, р=0.0004). Construction of ROC curves provided the quantitative values of study indexes, at which the risk of MVO increased. For BNP, this value was ≥276 pg/ml (sensitivity, 95.7 %; specificity, 37.9 %); for CK ≥160 U/l (sensitivity, 74.1 %; specificity, 61.9 %); and for IS ≥18.8 % (sensitivity, 79.3 %; specificity, 69.6 %). Correlation analysis of risk factors for increased size of the heterogeneity zone showed significant correlations of the heterogeneity zone size with older age of patients (r=0.544, р&lt;0.0001), higher concentrations of BNP (r=0.612, р&lt;0.0001), CK (r=0.3, 95 % CI: 0.02-0.5, р=0.03), and C-reactive protein (CRP) (r=0.59, CI: 0.3-0.7, р=0.0001). Increased levels of CK (r=0.53, 95 % CI: 0.29-0.70, р=0.0001) and BNP (r=0.55, 95 % CI: 0.28-0.70, p=0.0003) significantly correlated with increased IS.Conclusion Risk of MVO formation as per MRI data increased in the presence of type 2 DM and IS ≥18.8 % (р&lt;0.05). Formation of MVO in patients with STEMI was associated with increased levels of BNP ≥276 pg/ml and CK ≥160 U/l (р&lt;0.05). Increased levels of BNP, CK, and CRP were associated with a larger size of heterogeneity zone according to data of the correlation analysis. A larger heterogeneity zone was more typical for older patients. Increased levels of CK and BNP were also associated with larger IS. The correlation analysis did not show any significant interactions between the size of heterogeneity zone, IS, and MVO size (р&gt;0.05).

Identification of prognostic hypoxia-related genes signature on the tumor microenvironment in esophageal cancer.

Hypoxia is a crucial factor in the development of esophageal cancer. The relationship between hypoxia and immune status in the esophageal cancer microenvironment is becoming increasingly important in clinical practice. This study aims to clarify and investigate the possible connection between immunotherapy and hypoxia in esophageal cancer. The Cancer Genome Atlas databases are used to find two types of esophageal cancer cases. Cox regressions analyses are used to screen genes for hypoxia-related traits. After that, the genetic signature is validated by survival analysis and the construction of ROC curves. GSEA is used to compare differences in enrichment in the two groups and is followed by the CIBERSORT tool to investigate a potentially relevant correlation between immune cells and gene signatures. We found that the esophageal adenocarcinoma hypoxia model contains 3 genes (PGK1, PGM1, SLC2A3), and the esophageal squamous cell carcinoma hypoxia model contains 2 genes (EGFR, ATF3). The findings demonstrated that the survival rate of patients in the high-risk group is lower than in the lower-risk group. Furthermore, we find that three kinds of immune cells (memory activated CD4+ T cells, activated mast cells, and M2 macrophages) have a marked infiltration in the tissues of patients in the high-risk group. Moreover, we find that PD-L1 and CD244 are highly expressed in high-risk groups. Our data demonstrate that oxygen deprivation is correlated with prognosis and the incidence of immune cell infiltration in patients with both types of esophageal cancer, which provides an immunological perspective for the development of personalized therapy.

Comparative analysis of the levels of soluble forms of receptor and ligand of the immunity control point PD-1/PD-L1 in the blood serum of patients with typical bone osteosarcoma and chondrosarcoma.

Results of ELISA investigation of the pretreatment sPD-1 and sPD-L1 content in blood serum of 133 bone neoplasms patients aged 6-70 years and 57 practically healthy control persons aged 12-70 years are described. In 14 patients the neoplasms were of a benign character, in 16 - borderline giant-cell bone tumor was diagnosed, and in 103 - malignant bone lesions including 39 osteosarcomas and 42 chondrosarcomas were revealed. The sPD-1 receptor concentrations in blood serum did not differ between control healthy persons and primary bone tumor patients, while serum sPD-L1 level in bone tumor patients was statistically significantly increased (p<0.0000001). By means of ROC curve construction a cut-off sPD-L1 level of 16.5 pg/ml was found that imposed 75,9% sensitivity and 75,4% specificity in relation to healthy control. However, the frequency of sPD-L1 levels exceeding 16.5 pg/ml was approximately similar in benign, borderline and malignant bone tumor patients. Analysis of the pattern of sPD-1 and sPD-L1 circulation in the peripheral blood of patients with the most prevalent malignant bone tumors - osteosarcoma and chondrosarcoma - demonstrated that in both sarcoma types sPD-L1 level was significantly higher than in control, but in patients with chondrogenic tumors the soluble ligand sPD-L1 dominates in the circulation, while in those with osteogenic tumors - sPD-1 receptor prevails. In particular, sPD-1 level is statistically significantly higher in patients with typical osteosarcoma than in those with typical chondrosarcoma (p=0.002437), and sPD-L1/sPD-1 concentration ratio in chondrosarcoma is highly significantly more than 2-fold higher than in osteosarcoma (0.81 and 0.35 respectively; p=0.000284). The sensitivity of sPD-L1 ≥16.5 pg/ml test in typical osteosarcoma patients' group comprised only 70.2%, and in those with typical chondrosarcoma - 84.6%. Serum sPD-1 and sPD-L1 concentrations in osteosarcoma and chondrosarcoma patients were not associated with the indices of tumor advancement, its histological grade, localization in the osseous system, and type of affected bone. Thus, it can be concluded that the ratio between circulating soluble forms of the receptor and the ligand of PD-1/PD-L signaling pathway differs between patients with chondrogenic and those with osteogenic tumors, sPD-L1 being diagnostically valuable mostly for chondrogenic bone neoplasms.

Role of markers of inflammation and endothelial dysfunction in the prognosis of the development of cardiovascular complications in patients with coronary artery disease and metabolic syndrome after coronary stenting

Aim To study the role of inflammation markers and endothelial dysfunction in predicting the risk of cardiovascular event following a percutaneous coronary intervention (PCI) in patients with ischemic heart disease (IHD) and metabolic syndrome (MS).Materials and methods 80 patients (72 men; median age, 56 (50;63) years) with IHD and PCI were evaluated. Based on the presence of MS according to NCEP-ATP III criteria, patients were divided into two groups, group 1 without MS (n=32) and group 2 with MS (n=48). The control age- and sex-matched group included 15 people without cardiovascular diseases. Serum concentrations of tumor necrosis factor α (TNFα), interleukin 6 (IL-6), IL-10, lipoprotein-associated phospholipase A2 (LP-PLA2), and endothelin 1 were measured by enzyme-linked immunosorbent assay (ELISA). Patients were followed up for 12 months after PCI with evaluation of the incidence of adverse cardiovascular events. Statistical analysis was performed with Statistica 10.0 and Medcalc 19.2.6 software. Differences between variables were considered statistically significant at р&lt;0.05. Potential predictors were determined by the ROC analysis with construction of ROC curves, calculation of AUC (area under the curve), identification of COP (cut-off point by the Youden's index), and sensitivity (Se) and specificity corresponding to the COP.Results Patients with MS had statistically significantly higher serum levels of inflammatory markers than patients of the control group. Concentration of the intravascular inflammation marker, PL-PLA2, was 2.7 times higher in group 1 and 5.1 times higher in group 2 than in the control group (р&lt;0.001). Concentrations of endothelin 1 were 1.9 times higher in group 1 and 3.7 times higher in the MS group compared to the control. At one year after PCI, the incidence of adverse outcomes in the form of cardiovascular events was higher for patients with MS: 10 (20.8 %) cases of stent restenosis and 13 (27.1 %) episodes of coronary atherosclerosis progression according to results of repeated coronarography vs. 2 (6.3%) restenosis cases (χ2-10.853; р=0.002) and 2 (6.3%) episodes of atherosclerosis progression (χ2-23.651; р=0.001) for patients without MS. The groups did not differ in rates of myocardial infarction and cardiac death. The most significant predictors of unfavorable prognosis were LP-PLA2 concentration &gt;983.83 ng/ml (area under the ROC curve, 0.867; sensitivity, 80 %; specificity, 100%; р&lt;0.001) and endothelin 1 overexpression &gt;0.852 fmol/ml (area under the ROC curve, 0.885; sensitivity, 85.5 %; specificity, 83.6 %; р&lt;0.001).Conclusion Patients with MS were characterized by more pronounced imbalance of pro- and anti-inflammatory factors. Concentrations of LP-PLA2 &gt;983.83 ng/ml and endothelin 1 &gt;0.852 fmol/ml were shown to be predictors of unfavorable prognosis for patients with IHD and MS after PCI with coronary stenting.

Identification of a Plasma Microrna Signature as Biomarker of Subaneurysmal Aortic Dilation in Patients with High Cardiovascular Risk.

Patients with subaneurysmal aortic dilation (SAD; 25–29 mm diameter) are likely to progress to true abdominal aortic aneurysm (AAA). Despite these patients having a higher risk of all-cause mortality than subjects with aortic size <24 mm, early diagnostic biomarkers are lacking. MicroRNAs (miRs) are well-recognized potential biomarkers due to their differential expression in different tissues and their stability in blood. We have investigated whether a plasma miRs profile could identify the presence of SAD in high cardiovascular risk patients. Using qRT-PCR arrays in plasma samples, we determined miRs differentially expressed between SAD patients and patients with normal aortic diameter. We then selected 12 miRs to be investigated as biomarkers by construction of ROC curves. A total of 82 significantly differentially expressed miRs were found by qPCR array, and 12 were validated by qRT-PCR. ROC curve analyses showed that seven selected miRs (miR-28-3p, miR-29a-3p, miR-93-3p, miR-150-5p, miR-338-3p, miR-339-3p, and miR-378a-3p) could be valuable biomarkers for distinguishing SAD patients. MiR-339-3p showed the best sensitivity and specificity, even after combination with other miRs. Decreased miR-339-3p expression was associated with increased aortic abdominal diameter. MiR-339-3p, alone or in combination with other miRs, could be used for SAD screening in high cardiovascular risk patients, helping to the early diagnosis of asymptomatic AAA.

Combination of the anti‐apoptotic and pro‐apoptotic microRNAs expression and the anti‐apoptotic protein XIAP with serum CA19‐9 in the diagnosis of pancreatic adenocarcinoma

IntroductionPancreatic adenocarcinoma (PA) remains one of the most aggressive malignant tumors of the digestive tract, with a five‐year survival rate of 5%. Although early detection offers the best chance to cure pancreatic adenocarcinoma, early stage disease presents little or no symptoms. The most commonly used marker for early detection of AP is serum CA19‐9, which has a sensitivity of 70% to 80%, however, with a specificity less than 50%. MiRNAs, endogenous small RNAs of approximately 17–25 nucleotides, present an altered expression in various cancers, suggesting its close relationship to disease processes, with the possibility of being a molecular biomarker for diagnosis and prognosis of cancer.ObjectivesTo evaluate the effect of the combination of the association of anti‐apoptotic microRNAs: miR‐15a and miR‐16 and pro‐apoptotic microRNAs: miR‐21, miR‐221 and miR‐222 expression profile and the protein XIAP with serum CA19‐9 in diagnosis of diagnosis of pancreatic adenocarcinoma.Patients and MethodsWe studied 23 samples of PA and 20 as control samples: 13 of normal pancreatic tissue adjacent to the tumor (PPT), collected during pancreatic resections and 7 normal pancreas (NP) from deceased donors or patients who have undergone pancreatectomy affected by trauma. CA19‐9 was measured in serum and checked for expression of the miRNAs and XIAP in PA, PPT and NP through amplification by real‐time quantitative PCR (RT‐PCR). The usefulness of miRNAs and XIAP in the diagnosis of PA, alone or associated with CA19‐9, were analyzed by the construction of ROC curves.ResultsIt was observed significant differences in the expression of miR‐21 in the comparison between the PA and NP groups (p&lt;0.05). However, there was no significant difference in the expression of the protein XIAP between groups, as well as the expression of miR‐21 between groups NP and PPT. The combination of miR‐21 with CA19‐9 was more effective to discriminate the PA and NP (AUC‐ROC: 0.94; sensitivity: 78%, specificity: 99%) when compared with the assessments isolated.ConclusionThe expression of miR‐21 was demonstrated to be effective in discriminating between PA and NP and the association between miR‐21 and CA19‐9 increased the sensitivity and accuracy in the diagnosis of PA in the sample studied.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Diagnostic significance of volume capnography in examination of patients with bronchial asthma

Aim: to study the diagnostic significance of volume capnography in examination of patients with severe and moderate bronchial asthma (BA).&#x0D; Materials and Methods. 171 patents were examined, of them 43 patients with severe BA and 45 patients with moderate BA. The control group included 83 relatively healthy volunteers. In all the participants, along with clinical examination, parameters of spirometry and volume capnography were determined using ultrasound computer spirograph SpiroScout (Ganshorn, Germany) equipped with a volume capnography function.&#x0D; Results. Volume capnography revealed the following changes in patients with BA in comparison with the control group: increase in the slope of phase III (indicates non-uniformity of ventilation and perfusion in the lung periphery due to pathology of the small airways) and increase in emphysema index (indicates hyperinflation of lung). The above indices had statistically significant differences in severe and moderate asthma. Based on the results of examination of healthy individuals, the normal values for the slope of phase III (&lt;0.31 g/mol·L) and emphysema index (&lt;43) were calculated. Diagnostic sensitivity and specificity of volume capnography were studied with subsequent construction of ROC-curves and calculation of AUC for the slope angle of phase III and for emphysema index. It was found that most informative in BA are parameters of specificity of the diagnostic test (slope of phase III – 90.32%, emphysema index – 96.77%). The subsequent construction of ROC-curves showed that the AUC value for slope of phase III and emphysema index was higher in severe BA compared to the moderate BA (0.74 and 0.86, respectively).&#x0D; Conclusion. The obtained data demonstrate the significance of volume capnography in the functional diagnosis of respiratory disorders in BA.

Diagnostic significance of volume capnography in examination of patients with bronchial asthma

Aim: to study the diagnostic significance of volume capnography in examination of patients with severe and moderate bronchial asthma (BA).&#x0D; Materials and Methods. 171 patents were examined, of them 43 patients with severe BA and 45 patients with moderate BA. The control group included 83 relatively healthy volunteers. In all the participants, along with clinical examination, parameters of spirometry and volume capnography were determined using ultrasound computer spirograph SpiroScout (Ganshorn, Germany) equipped with a volume capnography function.&#x0D; Results. Volume capnography revealed the following changes in patients with BA in comparison with the control group: increase in the slope of phase III (indicates non-uniformity of ventilation and perfusion in the lung periphery due to pathology of the small airways) and increase in emphysema index (indicates hyperinflation of lung). The above indices had statistically significant differences in severe and moderate asthma. Based on the results of examination of healthy individuals, the normal values for the slope of phase III (&lt;0.31 g/mol·L) and emphysema index (&lt;43) were calculated. Diagnostic sensitivity and specificity of volume capnography were studied with subsequent construction of ROC-curves and calculation of AUC for the slope angle of phase III and for emphysema index. It was found that most informative in BA are parameters of specificity of the diagnostic test (slope of phase III – 90.32%, emphysema index – 96.77%). The subsequent construction of ROC-curves showed that the AUC value for slope of phase III and emphysema index was higher in severe BA compared to the moderate BA (0.74 and 0.86, respectively).&#x0D; Conclusion. The obtained data demonstrate the significance of volume capnography in the functional diagnosis of respiratory disorders in BA.

Susceptibility mapping of instability related to shallow mining cavities in a built-up environment

Anthropogenic activities and urbanization frequently spread over areas underlain by unstable karst ground or man-made cavities, leading to potential risk situations for buildings, infrastructure and population. The roof of the cavities may rapidly propagate upwards, eventually resulting in progressive ground settlement and/or sudden collapse. These processes are frequently accelerated or triggered by various human activities (e.g., overloading, water recharge, water table decline). In this paper, the susceptibility to instability of artificial cavity networks under an urban area in Apulia Region, Southern Italy, was assessed and evaluated. Here, there is dense network of underground quarries excavated for the extraction of massive calcarenite for building and ornamental stone that are currently affected by severe instability problems. Identifying the zones of the cavities most prone to instability is of great practical importance. Susceptibility models have been developed analyzing the statistical relationships between the cavity sections with evidence of instability and a number of predisposing factors mainly related to the 3D geometry of the voids, roof thickness and the presence of overloads. The models produced by the discriminant analysis and the logistic regression approaches were independently and quantitatively evaluated through the construction of ROC curves. Although the two models are characterized by different input data treatment, as the logistic regression allows using continuous and discrete variables or any combination of both types even if they do not have a normal distribution, the ROC curves highlighted, for both methods, a satisfactory congruence between the model results and the observed data. Consequently, from the model performance analysis, the two models were evaluated comparable in terms of result reliability. The methodology should be considered as a general first-level analysis for near surface underground cavities aimed at identifying critical cave sectors that can be the focus of more detailed analyses, especially those associated with sensitive zone related to the presence of buildings, roads and frequent presence of human activity.

Genome-Wide Analysis of Genetic Associations for Prediction of Polygenic Hypercholesterolemia with Bayesian Networks

The genome-wide analysis of genetic associations with lipid metabolism indicators was carried out using the technology of Bayesian networks (BN). It was performed to diagnose polygenic hypercholesterolemia on the basis of genetic data of the Russian population of patients. The data of 1,200 patients was analyzed. 196725 SNPs as well as clinical data, lipid profile indicators -- different types of cholesterol -- were obtained for each of them. The genome-wide association analysis (GWAS) and the statistical method of Pearson's chi-squared test were used for the initial selection of the most significant parameters. Two of the patient states related to a lipid metabolism were studied. These states are the level of LDL-C (low density lipoprotein) and the level of HDL-C (high density lipoprotein). The Bayesian networks having the simplest topology -- naive -- were used to predict the level of lipoprotein. The construction of ROC-curves and the calculation of the area under these curves (AUC) were used to assess a quality (reliability) of the prediction. AUC value increased from 0,5 for the initial BN to 0,9 after selecting of significant parameters using the GWAS method or the Pearson one. A further increase in AUC to 0,99 and decrease in the number of prognostic parameters to 150 was performed using Bayesian network optimization with respect to the number of parameters-nodes. Here the optimized function was value of AUC. The ambiguity of obtaining prognostic parameters at various ways of initial reducing the number of network nodes using the methods of GWAS and Pirson is shown. Low values of AUC were obtained for an independent control group of patients, despite very good results on the quality of the predictions, which were obtained on the training set. Further application of the proposed methodology is possible after the substantial reduction of the number of SNPs on the base of the analysis of the respective molecular mechanisms.